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  • Pihl, MikaelLinköpings universitet,Pediatrik,Hälsouniversitetet (author)

Regulatory T cell phenotype and function 4 years after GAD–alum treatment in children with type 1 diabetes

  • Article/chapterEnglish2013

Publisher, publication year, extent ...

  • 2013-04-18
  • Wiley-Blackwell,2013
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:liu-93379
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-93379URI
  • https://doi.org/10.1111/cei.12078DOI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Funding Agencies|Swedish Research Council|K2008-55x-20652-01-3|Swedish Child Diabetes Foundation (Barndiabetesfonden)||Medical Research Council of Southeast Sweden||JDRF|1-2008-106|Ile-de-France CODDIM||Inserm Avenir Program||
  • Glutamic acid decarboxylase (GAD)65 formulated with aluminium hydroxide (GAD-alum) was effective in preserving insulin secretion in a Phase II clinical trial in children and adolescents with recent-onset type 1 diabetes. In addition, GAD-alum treated patients increased CD4+CD25hi forkhead box protein 3+ (FoxP3+) cell numbers in response to in-vitro GAD65 stimulation. We have carried out a 4-year follow-up study of 59 of the original 70 patients to investigate long-term effects on the frequency and function of regulatory T cells after GAD-alum treatment. Peripheral blood mononuclear cells were stimulated in vitro with GAD65 for 7 days and expression of regulatory T cell markers was measured by flow cytometry. Regulatory T cells (CD4+CD25hiCD127lo) and effector T cells (CD4+CD25–CD127+) were further sorted, expanded and used in suppression assays to assess regulatory T cell function after GAD-alum treatment. GAD-alum-treated patients displayed higher frequencies of in-vitro GAD65-induced CD4+CD25+CD127+ as well as CD4+CD25hiCD127lo and CD4+FoxP3+ cells compared to placebo. Moreover, GAD65 stimulation induced a population of CD4hi cells consisting mainly of CD25+CD127+, which was specific of GAD-alum-treated patients (16 of 25 versus one of 25 in placebo). Assessment of suppressive function in expanded regulatory T cells revealed no difference between GAD-alum- and placebo-treated individuals. Regulatory T cell frequency did not correlate with C-peptide secretion throughout the study. In conclusion, GAD-alum treatment induced both GAD65-reactive CD25+CD127+ and CD25hiCD127lo cells, but no difference in regulatory T cell function 4 years after GAD-alum treatment.

Subject headings and genre

  • CD4 T cells (T helper
  • Th0
  • Th1
  • Th2
  • Th3
  • Th17)
  • diabetes
  • immune regulation
  • regulatory T cells (Treg)
  • therapy/immunotherapy
  • MEDICINE
  • MEDICIN

Added entries (persons, corporate bodies, meetings, titles ...)

  • Åkerman, LindaLinköpings universitet,Pediatrik,Hälsouniversitetet(Swepub:liu)linak20 (author)
  • Axelsson, StinaLinköpings universitet,Pediatrik,Hälsouniversitetet(Swepub:liu)stiax77 (author)
  • Chéramy, MikaelLinköpings universitet,Pediatrik,Hälsouniversitetet(Swepub:liu)mikch88 (author)
  • Hjorth, MariaLinköpings universitet,Pediatrik,Hälsouniversitetet(Swepub:liu)marhe44 (author)
  • Mallone, R.St Vincent Paul Hospital, France (author)
  • Ludvigsson, JohnnyÖstergötlands Läns Landsting,Linköpings universitet,Pediatrik,Hälsouniversitetet,Barn- och ungdomskliniken i Linköping(Swepub:liu)johlu29 (author)
  • Casas, RosauraLinköpings universitet,Pediatrik,Hälsouniversitetet(Swepub:liu)rosca56 (author)
  • Linköpings universitetPediatrik (creator_code:org_t)

Related titles

  • In:Clinical and Experimental Immunology: Wiley-Blackwell172:3, s. 394-4020009-91041365-2249

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